This application represents the creation of a Specialized Program of Research Excellence (SPORE) in Gastrointestinal Cancer originating from the Gastrointestinal (Gl) Malignancies Program of the Dana- Farber/Harvard Cancer Center (DF/HCC). The main goal of the DF/HCC SPORE in Gl Cancer is the translation of biological and technological advances into improvements in prevention, diagnostics, predictors of outcome, and advances in the treatment of gastrointestinal malignancies. The DF/HCC SPORE in Gl Cancer includes researchers from all Harvard-affiliated hospitals: the Dana-Farber Cancer Institute, the Brigham and Women's Hospital, the Massachusetts General Hospital, the Beth Israel Deaconess Medical Center, Children's Hospital of Boston, and Harvard School of Public Health. Five major projects are proposed including: 1) Improved pre-operative staging of pancreatic cancer; 2) Molecular fluorescent imaging for the early detection of colorectal neoplasms; 3) Defining optimal doses of vitamin D for chemoprevention in Blacks; 4) The role of PI3-Kinase signaling pathway in defining sensitivity and resistance to anti-EGFR therapy in colorectal cancer; and 5) Targeted therapy resistance mechanisms in gastrointestinal stromal tumor. These projects will be integrated by the creation of four cores: 1) Administration, Evaluation & Planning; 2) Tissue and Pathology; 3) Biostatistics and 4) Genomics and Bioinformatics. The SPORE application outlines a Developmental Projects Program that includes a plan or selection of new projects as well as nine pilot projects that could be supported. We also include a Career Development Award Program that outlines a mechanism for the identification and support of talented young investigators in Gl cancer. The projects and cores proposed in this application are highly integrated with present DF/HCC core resources, and involve key collaborations with investigators from other existing SPOREs. The creation of this Gl SPORE at DF/HCC will combine leading Harvard researchers in basic, translational, and clinical sciences into a program that has the focus and coordination required to produce meaningful advances in the diagnosis, treatment, and prevention of Gl cancers.